A general method for solubilizing peptides in either organic or aqueous solution is presented. The peptide is coupled to a hydrophobic polymer (oil soluble), which can be readily cleaved to a hydrophilic (water soluble) polymer. Poly(tert-butyl acrylate) (RBA) was synthesized via a living anionic polymerization of tert-butyl acrylate (tBA) by LiCl-complexed (diphenylhexyl)lithium in tetrahydrofuran (THF) at -78 degrees C and terminated by carbon dioxide or succinic anhydride. The carboxyl-terminal PtBA was coupled to alanine ethyl ester in only 40% yield by a conventional peptide synthesis method using 1,3-dicyclohexylcarbodiimide (DCC) as the coupling reagent. However, PtBA terminated by succinic anhydride could be coupled to alanine ethyl ester in 94% yield, to alanylalanylalanine methyl ester in 83% yield, and to N-im-tosylhistidine methyl ester in 81% yield. The tosyl protecting group on the latter was completely removed to give histidine-terminated PtBA, These alanine- and histidine-terminated PtBAs were quantitatively hydrolyzed to poly(acrylic acid) (PA). These peptides were soluble in solvents ranging from nonpolar hexane to water depending on the nature of the attached polymer chain.